TBBPA, a brominated derivative of bisphenol A, is the highest-selling brominated flame retardant. From the structural resemblance to the thyroid hormone (TH), TBBPA interferes with TH binding to the plasma protein transthyretin and with TH action through TH receptors.

Discovery

Brominated flame retardants have been routinely used for several decades to prevent the ignition of combustible organic materials. Meerts et al.1 first reported that TBBPA affects TH binding to human transthyretin in vitro in 2000.

Properties 

Molecular formula, C15H12Br4O2; Mr. 543.88; physical state, crystalline or powdered white solid; water solubility, 0.063mg/L at 21°C;2 LogKow 5.9;2 pKa 7.5 and 8.5. 

Usage 

TBBPA was introduced as a substitute for PBDEs. It is a flame retardant bound to epoxy and polycarbonate resins in printed circuit boards and casings usedin personal computers, printers, faxmachines, and copiers. It is an additive flame retardant of acrylonitrile-butadiene-styrene resin and polystyrene that contains dimethyl TBBPA in automotive parts, pipes and fittings, domestic and office appliances, packaging, electrical and electronic equipment enclosures, furniture, and construction materials.3 TBBPA is produced in China, Israel, Japan, Jordan, and the United States, but no longer in the European Union (EU).

Origins of environment and biota TBBPA Anthropogenic, primarily from waste streams or effluents of manufacturing plants using TBBPA. TBBPA is also detected in sewage sludge and landfill leachate.

Action mechanisms 

TBBPA also has adverse effects on reproductive and immune functions. However, there is still controversy over these effects. The EU concludes that TBBPA shows no risk to human health or the environment.

In vitro and in vivo assays for the detection of thyroid system disruption activity of TBBPA

(1) In vitro cell-based assays. Competitive TTR binding assay (～10 times more potent than TH); Competitive TR binding assay (effective at submicromolar concentrations); TH-response reporter gene assay in Xenopus, Chinese hamster, rat, and yeast cells (weak agonist and antagonist activities at 0.1–1.0μM); T-screen (rat GH3 cell growth assay, effective at 10μM); a yeast two-hybrid assay (effective at 10^{- 6}– 10^-5 M); a cultured frog tadpole tail fin biopsy assay (C-fin assay; no effects at 0.01–1.0μM).

(2) In vivo or ex vivo assays. Amphibian Xenopus laevis metamorphosis assays: inhibition of larval development at 920 nM for 21 days; weak agonist and antagonist activities on TH-responsive gene activation at 920 nM for 1–3days, and at 0.184–0.92 nM for 1 day using St 52 tadpoles. Transgenic tadpole assays harboring thibz-luc and thibz-gfp genes: antagonist activity at 1μM with 5 nM T3, and at 1μM with 10 nM T3, respectively.